Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Brain Res Bull. Author manuscript; available in PMC Feb 16, 2010.
Published in final edited form as:
PMCID: PMC2656644
NIHMSID: NIHMS96456

The Thalamostriatal Systems: Anatomical and Functional Organization in Normal and Parkinsonian States

Abstract

Although we have gained significant knowledge in the anatomy and microcircuitry of the thalamostriatal system over the last decades, the exact function(s) of these complex networks remain(s) poorly understood. It is now clear that the thalamostriatal system is not a unique entity, but consists of multiple neural systems that originate from a wide variety of thalamic nuclei and terminate in functionally segregated striatal territories. The primary source of thalamostriatal projections is the caudal intralaminar nuclear group which, in primates, comprises the centromedian and parafascicular nuclei (CM/Pf). These two nuclei provide massive, functionally organized glutamatergic inputs to the whole striatal complex. There are several anatomical and physiological features that distinguish this system from other thalamostriatal projections. Although all glutamatergic thalamostriatal neurons express vGluT2 and release glutamate as neurotransmitter, CM/Pf neurons target preferentially the dendritic shafts of striatal projection neurons, whereas all other thalamic inputs are almost exclusively confined to the head of dendritic spines. This anatomic arrangement suggests that transmission of input from sources other than CM/Pf to the striatal neurons is likely regulated by dopaminergic afferents in the same manner as cortical inputs, while the CM/Pf axo-dendritic synapses do not display any particular relationships with dopaminergic terminals. A better understanding of the role of these systems in the functional circuitry of the basal ganglia relies on future research of the physiology and pathophysiology of these networks in normal and pathological basal ganglia conditions. Although much remains to be known about the role of these systems, recent electrophysiological studies from awake monkeys have provided convincing evidence that the CM/Pf-striatal system is the entrance for attention-related stimuli to the basal ganglia circuits. However, the processing and transmission of this information likely involves intrinsic GABAergic and cholinergic striatal networks, thereby setting the stage for complex physiological responses of striatal output neurons to CM/Pf activation. Finally, another exciting development that will surely generate significant interest towards the thalamostriatal systems in years to come is the possibility that CM/Pf may be a potential surgical target for movement disorders, most particularly Tourette syndrome and Parkinson's disease. Although the available clinical evidence is encouraging, these procedures remain empirical at this stage because of the limited understanding of the thalamostriatal systems.

Keywords: Parkinson's disease, thalamus, striatum, glutamate transporter, synaptic plasticity

INTRODUCTION

Vogt and Vogt [94] first suggested the existence of the thalamostriatal system, but the pioneering data of Powell and Cowan [69] showing profuse striatal projections from the whole intralaminar nuclear complex in primates were the true starting point for extensive anatomical studies of this projection in various species. Since then, the anatomical and functional organization of this system and its potential role in regulating neurotransmitter homeostasis in the basal ganglia under normal and pathological conditions has been examined. Studies in our laboratory and others have emphasized the precise topographical arrangement and synaptic organization of these projections in primates. The use of modern and sensitive tracing methods has demonstrated that the thalamostriatal systems have multiple origins that extend beyond the caudal intralaminar thalamic nuclei to include specific and non-specific thalamic nuclear groups, suggesting the existence of multiple thalamostriatal systems (Table 1). The recent cloning of the vesicular glutamate transporters 1 and 2 (vGluT1 and vGluT2) [20a], and the insight that these are differentially distributed between thalamic and cortical inputs to the striatum has provided us with unique tools to examine and compare the synaptology and plasticity of the corticostriatal and thalamostriatal systems in normal and pathological conditions. In the following account, we will discuss anatomical and functional characteristics of the thalamostriatal systems and review recent findings on the plasticity of the thalamostriatal projections the nonhuman primate model of Parkinson's disease. The implication of these findings on the development of surgical or pharmacological therapies for movement disorders aimed at targeting the thalamostriatal systems will be discussed. Readers are referred to previous reviews for additional information and a broader coverage of early literature on the thalamostriatal projections [25,26,40,58,59,66,88,91]

Table 1
Summary of key differences between the thalamostriatal systems that originate from CM/Pf versus other thalamic nuclei.

ORIGIN AND ANATOMICAL ORGANIZATION OF THE THALAMOSTRIATAL SYSTEMS

The main source(s) of thalamostriatal projections are the intralaminar thalamic nuclei, but substantial inputs from midline and specific relay nuclei have also been described in various species [9,11,16,17,19,25,45,56-59,66,67,70,73-75,87,88]. The topography of thalamostriatal projections in rats has been studied in detail, and has been summarized in previous reviews [25,88]. In monkeys, tracing studies have mainly focused on the organization of projections from the caudal intralaminar nuclei, the centre median and parafascicular nuclei (CM/Pf). Based on its striatal targets, the CM/Pf complex is divided into five major compartments in primates: (1) The rostral third of Pf projects predominantly to the nucleus accumbens, (2) the caudal two thirds of Pf innervates the caudate nucleus, (3) the dorsolateral extension of Pf (Pfdl) projects to the anterior putamen, (4) the medial two thirds of CM (CMm) projects to the post-commissural putamen and (5) the lateral third of CM (CMl) projects to the primary motor cortex (Fig. 1). Through these topographic and specific projections, the CM/Pf influences widespread striatal regions involved in processing functionally segregated information: The rostral Pf is mainly related to the limbic striatum, the Pf/Pfdl is preferentially connected with associative striatal territories, whereas the CMm is the main source of inputs to sensorimotor striatal regions (Fig.1) [88].

Figure 1
Color-coded summary of the various sub-compartments of the CM/PF complex with their main striatal-receiving territories in monkeys. The antero-posterior stereotaxic coordinates of the striatal and CM/PF sections are indicated. The lateral part of CM (CMl) ...

Thalamostriatal projections also arise from midline and specific thalamic nuclei. In rats, projections from midline thalamic nuclei are mainly confined to the ventral striatum, but they also provide significant inputs to dorsal striatal regions [88]. In primates, it has recently been emphasized that a significant non-intralaminar source of thalamostriatal projections originates from the ventral motor thalamic nuclei [26,56,57,88]. Interconnected regions of the ventral motor thalamic nuclei and motor cortices send convergent inputs to the sensorimotor striatum suggesting functional interactions between corticostriatal and thalamostriatal projections in motor behaviors [57]. Several other thalamic nuclei have been recognized as potential sources of thalamostriatal projections in nonhuman primates [87], but details on the topography and intrastriatal arborization of these projections is scarce and will not be discussed further in this review (see ref. 88 for details).

THALAMOSTRIATAL VERSUS THALAMOCORTICAL SYSTEMS: SEGREGATED ORIGINS OR COLLATERALIZED PROJECTIONS?

There is agreement among retrograde double labeling studies that a substantial proportion of neurons in the rostral intralaminar nuclear group and some specific thalamic nuclei (ventral motor nuclei, mediodorsal nucleus) provide axon collaterals to both the striatum and the cerebral cortex, while thalamostriatal and thalamocortical neurons are largely segregated in the caudal intralaminar CM/Pf nuclear complex [25,73,88]. As mentioned above, CM projections to the primary motor cortex in monkeys arise mainly from a neuronal population confined to the lateral part of CM [88], whereas neurons in the medial CM project to the post-commissural putamen (Fig. 1).

However, recent single cell filling data have demonstrated a more complex hodology of CM/Pf neurons, and revealed significant differences in the degree of arborization of thalamostriatal neurons from Pf between rats and monkeys. In rats, most Pf neurons that project to the caudate-putamen complex send sparse collaterals to the cerebral cortex [16]. This projection pattern differs from that of projections from the centrolateral nucleus, which provide scarce loosely organized long varicose processes to the striatum, but form dense patches of terminals in the rat cortex [17]. The projection pattern of individual CM neurons is different and more complex in nonhuman primates [67]. Three major groups of CM neurons have been identified based on their extent of projections to the striatum and cerebral cortex in monkeys: More than half of all neurons innervate densely and focally the striatum without any significant input to the cerebral cortex, about one third of neurons innervate diffusely the cerebral cortex, without any significant projection to the striatum, and the remaining neurons project to both targets.

In contrast to retrograde labeling studies that revealed a strict regional pattern of localization of CM-striatal vs CM-cortical neurons (Fig. 1), the three main subtypes of CM neurons described in the anterograde single-cell labeling study appear to be randomly distributed in CM [67]. This discrepancy may be explained by the overall scarcity of the diffuse CM-cortical projections compared to the dense and highly focused CM-striatal system (Fig. 2). The small amount of CM terminals in the cerebral cortex may not be enough to take up the minimum amount of tracer needed to retrogradely label most CM-cortical projections, except those that originate from neurons in the lateral part of CM (CMl) (Figs 1,,22).

Figure 2
Summary of the general pattern of CM inputs to the striatum and the cerebral cortex. Although a significant proportion of single CM neurons innervate both regions, CM-striatal projections are more massive and give rise to more profuse and focussed fields ...

SYNAPTIC TARGETS OF THE THALAMOSTRIATAL SYSTEMS

Electron microscopic data from tract-tracing studies in rats and monkeys have provided detailed information on the synaptic microcircuitry of the thalamostriatal system. These studies have mainly focused on the thalamostriatal system originating in CM/Pf. The main characteristic feature of this system is the preponderance of inputs from CM/Pf neurons to dendritic shafts of striatal projection neurons (Fig. 3) and interneurons [18,70,74,82,88], although a small subset of neurons in the rat Pf appears to preferentially target dendritic spines [45]. Both “direct and indirect” striatofugal neurons are contacted by CM/Pf projections [11,46,82], but electron microscopic studies in monkeys have suggested a preferential innervation of `direct pathway' striatal neurons, projecting to the internal globus pallidus (GPi), compared to `indirect pathway' striatal projecting neurons, projecting to the external globus pallidus (GPe) [82]. However, this does not mean that the intralaminar nuclei do not influence striatal projection neurons that give rise to the `indirect pathway': Pf lesions in rats with prior lesions of the nigrostriatal tract reduce enkephalin mRNA expression in indirect striatofugal neurons, without significantly affecting substance P mRNA expression in direct pathway neurons [4], suggesting that Pf inputs to the striatum may influence striatal activity in a complex, perhaps multisynaptic manner that is not immediately predicted by anatomical studies.

Figure 3
Summary of results from anterograde tracing studies of thalamic projections to the rat striatum. The histogram illustrates the percentage of labeled boutons from each of the thalamic or cortical (M1) regions injected. Apart from Pf, all other thalamic ...

In monkeys, most striatal interneurons, except those that express calretinin, receive direct CM inputs, but the cholinergic interneurons seem to be preferential target of these projections [48,60,83]. In rats, parvalbumin-containing GABAergic interneurons are devoid of Pf inputs [73a], suggesting a possible species difference in the thalamic regulation of these `fast spiking' interneurons between primates and rats [88]. Despite strong monosynaptic innervation from the caudal intralaminar nuclei, CM stimulation results predominantly in reduced firing of tonically active neurons (TANs; likely corresponding to cholinergic interneurons) and decreased acetylcholine release in the rat and monkey striatum [64b,98; see below].

As mentioned before, thalamostriatal projections from CM/Pf and from other thalamic areas differ with regard to their synaptic targets in the striatum, and, related to this, with regard to their relationship with dopaminergic inputs. In contrast to cortical terminals that frequently form convergent axo-spinous synapses with dopaminergic terminals, CM axo-dendritic synapses do not display specific synaptic relationships with dopaminergic afferents on striatal neurons [86]. On the other hand, striatal inputs from relay, associative and rostral intralaminar thalamic nuclei form almost exclusively axo-spinous synapses (Fig. 3) that often converge with dopaminergic inputs onto individual spines in the rat caudate-putamen [64a,70]. Therefore, except for CM/Pf axo-dendritic afferents, dopaminergic inputs are located to provide tight regulation of other thalamic and cortical axo-spinous glutamatergic afferents in the striatum [5,85].

THALAMIC REGULATION OF STRIATAL RELEASE OF NEUROMODULATORS

Considerable attention has been paid at the role of CM/Pf effects on dopamine functions in the striatum. In anesthetized rats and cats, Pf lesions reduce dopamine utilization [38,65], and increase striatal dopamine uptake [77] and dopamine D2-receptor density [39]. Infusion of GABA into the cat CM/Pf reduces dopamine release [72]. There is some controversy regarding the effects of electrical Pf stimulation on striatal dopamine release, some studies demonstrating a reduction of striatal dopamine release in cats [12], while others show increased striatal dopamine utilization (without changing dopamine levels) in rats [39]. Some of the modulation of dopamine levels with electrical stimulation of Pf may be due to inadvertent involvement of the fasciculus retroflexus that contains descending inhibitory projections from the lateral habenula to dopaminergic SNc neurons [22,55]. However, since fiber-sparing Pf lesions also affect striatal dopaminergic functions [37,38], it is likely that CM/Pf neurons per se mediate some of these effects. Because there is no direct axo-axonic synapses between thalamic and dopaminergic terminals in the striatum, these effects are probably mediated through complex polysynaptic routes that may involve transcortical systems and/or intrinsic striatal microcircuits [34,35]. The thalamostriatal projection from CM/Pf may also play roles in dopamine D1-receptor-mediated stimulation of striatal acetylcholine release [13] and c-fos gene expression [24]. CM/Pf inputs may also modulate striatal D2-receptor mediated long term depression [95].

Several studies have also described effects of CM/Pf interventions on striatal serotonergic transmission [8,77]. As described below, CM/Pf stimulation decreases acetylcholine, but increases GABA release in rat and monkey striatum [64b,98]. There is a significantly increased expression of the astrocytic glutamate transporter, GLT-1, combined with a corresponding reduction of extracellular glutamate levels in the rat striatum after cortical, but not thalamic, deafferentation [50,51].

VESICULAR GLUTAMATE TRANSPORTERS 1 AND 2 - SELECTIVE MARKERS OF CORTICOSTRIATAL AND THALAMOSTRIATAL SYSTEMS

In recent years, there has been increasing evidence that the vesicular glutamate transporters vGluT1 and vGLUT2 can be used as selective markers for the corticostriatal and thalamostriatal systems, respectively. The selective labeling has helped us to further understand the synaptic organization of the two major glutamatergic projection systems in the rat and monkey striatum under normal and parkinsonian conditions. Despite strong evidence for complete segregation of vGluT1 and vGluT2 proteins at the terminal level in the rat and monkey striatum [44,70,71,71a], the mRNA and protein for these markers partly co-localize in neuronal cell bodies of thalamostriatal neurons in the rat ventral thalamus, but not in intralaminar and midline thalamic nuclei [6,7,7a]. The significance of this partial co-expression of the two vGluTs at the cell body level on the relative distribution of vGluT1 and vGluT2 immunoreactivity in thalamostriatal terminals remains to be determined.

In monkeys and rats, more than 95% vGluT1-immunoreactive (presumably corticostriatal) terminals target dendritic spines, while vGluT2-containing thalamostriatal terminals display a more heterogeneous pattern of synaptic connectivity that differs between primates and nonprimates: 70% of the vGluT2-positive boutons contact dendritic spines in rats, whereas only about 50% do so in the monkey striatum [70]. Terminals positive for vGluT2 can be further divided by their nucleus of origin. It has been shown that vGluT2-positive CM/Pf terminals form predominantly axo-dendritic synapses, while vGluT2-containing thalamostriatal terminals from rostral intralaminar, relay and associative thalamic nuclei target almost exclusively dendritic spines [70]. In rats, the relative abundance and pattern of synaptic connectivity of vGluT2 terminals varies significantly between the patch and matrix compartments; almost 90% vGluT2 terminals form axo-spinous synapses in patches, but only about 50-70% do so in the matrix suggesting a strikingly different synaptology of the thalamostriatal system between these two striatal compartments [21,70]. This difference is accounted for by the large proportion of vGluT2 terminals from Pf that form axo-dendritic synapses in the matrix compartment, while avoiding patches [74,88]. In both rats and monkeys, about 20% of the putative glutamatergic terminals that form asymmetric synapses do not express vGluT1 or vGluT2 suggesting that another, as yet undetermined vGluT may exist [44,71]. Although vGluT3 is expressed in the striatum, it is mainly found in non-glutamatergic terminals and post-synaptic dendrites [20,24a], thereby cannot account for the vGluT1-/vGluT2-negative striatal terminals described above.

SYNAPTIC REORGANIZATION OF THALAMOSTRIATAL AND CORTICOSTRIATAL GLUTAMATERGIC SYSTEMS IN PARKINSON'S DISEASE

VGluT1 and vGluT2 were recently used to examine changes in the synaptic organization of the corticostriatal and thalamostriatal systems in MPTP-treated parkinsonian monkeys [71]. No significant change in the overall pattern of synaptic connectivity and relative prevalence of vGluT2 thalamostriatal terminals were found in the caudate nucleus and putamen of dopamine-depleted monkeys, while there was a significant increase in the relative abundance of vGluT1 immunoreactivity [71]. These findings have been recently confirmed in postmortem human brain tissue showing vGluT1 protein increase in the putamen of patients with Parkinson's disease [36]. At first glance, these observations are at odds with evidence for significant loss of spines in the striatum of MPTP-treated parkinsonian monkeys [92], 6-OHDA-treated rats [32,33] and human PD patients [89]. However, unbiased stereological studies are needed to demonstrate a genuine increase in the total number vGluT1-immunoreactive terminals and characterize potential remodeling of the synaptology of vGluT1-immunoreactive boutons in the striatum of parkinsonian monkeys. Although no clear change in the abundance of vGluT2 terminals was found in various striatal territories of MPTP-treated monkeys, the ratio of axo-spinous to axo-dendritic synapses was substantially increased in the post-commissural putamen of these animals [71]. This change in the synaptic connectivity of vGluT2 terminals may be the result of cell loss in CM which, as discussed below, has been found to degenerate in Parkinson's disease and in some rodent models of parkinsonism (see below).

AFFERENTS TO THALAMOSTRIATAL NEURONS

The main inputs to thalamostriatal neurons originate from the basal ganglia output nuclei, the GPi and the substantia nigra pars reticulata (SNr), and from the brainstem. In monkeys, GPi and SNr provide massive and topographic projections to the caudal intralaminar complex that form direct synaptic contacts with thalamostriatal neurons [81]. This projection system originates from axon collaterals of the basal ganglia-thalamocortical system that terminate mainly in the ventrobasal nuclear group. In turn, both nuclei send highly topographic and specific inputs to different functional territories of the striatum [25,79,82,88] (Fig. 1). In monkeys, functionally segregated outputs from GPi largely innervate different regions of CM/Pf [79,88], while projections from SNr are confined to the Pf. Together, these anatomical data provide a substrate for the formation of functionally segregated basal ganglia-thalamostriatal loops in primates (Fig. 1). The anterior intralaminar nuclei also receive subcortical inputs from various brainstem, cerebellar, and spinal cord nuclei, as well as inputs from the amygdala, superior colliculus, and pretectal nuclei [58], but direct evidence for synaptic innervation of thalamostriatal neurons is lacking. Brainstem cholinergic and monoaminergic inputs from the pedunculopontine nucleus, raphe nuclei, and locus coeruleus have also been established. Projections from the pedunculopontine nucleus are mainly directed toward Pf and display a high degree of chemical heterogeneity using acetylcholine, GABA, and glutamate as co-existing neurotransmitters [80,88]. The reticular formation (RF) also provides massive inputs to anterior and posterior intralaminar nuclei. By virtue of these strong associations with the RF, the intralaminar nuclei are traditionally seen as part of the “reticular activating system” that regulates the mechanisms of cortical arousal and attention [41].

FUNCTIONAL PROPERTIES OF CM/Pf THALAMOSTRIATAL NEURONS

The exact functional role of the thalamostriatal system remains poorly understood. Kimura and his colleagues have proposed that CM and Pf supply striatal neurons with information that have attentional values, thus acting as detectors of behaviorally significant events occurring on the contralateral side [40,61,62,88], which is consistent with positron emission tomographic data in humans showing activation of the CM/Pf complex when participants switch from a relaxed awake state to an attention-demanding reaction-time task [41]. Two main functional characteristics of CM/Pf neurons have been identified in monkeys. First, CM/Pf neurons have multimodal properties, ie they respond to a large variety of sensory stimuli (auditory, visual, somatosensory) presented either in or outside sensorimotor conditioning tasks. Second, CM/Pf neurons are temporally tuned, i.e., they can generate in a timely fashioned manner discrete responses to a wide variety of sensory stimuli [61,62]. On the basis of their latency and pattern of responses to sensory stimuli, CM/Pf neurons have been categorized into two main populations, namely those that display short-latency facilitatory responses (SLF neurons) or long-latency facilitatory responses (LLF) to sensory events. These two populations are largely segregated in the CM/Pf complex, SLF neurons being mainly found in Pf, whereas LLF are particularly abundant in CM [40,61,62,88]. Responses of both types of neurons are not associated with reward. On the contrary, the magnitude of CM/Pf neuronal responses is larger when the stimulus is unpredictable and different from expectations [62]. For instance, a majority of CM neurons fire when a small-reward action is required, but a large-reward option is anticipated [62]. This contrasts them from the tonically active neurons (TANs; putative striatal cholinergic interneurons); one of their main targets in the striatum (see above), which under the same experimental conditions, respond preferentially to rewarding stimuli [1,13a,54]. However, CM/Pf inputs are required for the expression of the sensory responses of TANs acquired through sensorimotor learning. Inactivation of CM/Pf decreases the characteristic pause and subsequent rebound facilitation, but does not affect the early short latency facilitation, of TANs in response to sensorimotor conditioning [40,54,88]. Taken into consideration the importance of the dopaminergic system in modulating striatal activity through TANs, one may suggest that the behaviorally sensory events transmitted along the thalamostriatal projection from CM/Pf, in coordination with the motivational value of the dopamine inputs, provide a strong basis for proper selection of actions through the basal ganglia thalamocortical/striatal circuitry [40,54,88]. Therefore, based on their strong physiological responses to unanticipated small-reward action, CM/Pf neurons may complement decision and action bias through the thalamostriatal system and basal ganglia- thalamocortical functional loops [13a,62].

EFFECTS OF CM STIMULATION UPON STRIATAL ACTIVITY

The paucity of functional studies of the thalamostriatal systems limits considerably our understanding of these projections in the functional circuitry of the basal ganglia. Our recent primate in vivo recordings of changes in the activity of striatal neurons induced by electrical stimulation of CM addressed this issue [64b]. All striatal cells tested in this study responded to burst stimulation (100 Hz, 1 sec, 100-175 μA) of the CM with a delay of tens of milliseconds after the onset of the stimulation trains. Phasically active neurons (PANs-likely medium spiny projection neurons) responded mainly with early increases in firing, while most tonically active neurons (TANs; likely cholinergic interneurons), displayed combinations of increases and decreases in firing (Fig.4). These changes in neuronal activity were accompanied by a GABA-mediated decrease in striatal acetylcholine. Based on these studies, it appears that striatal responses to CM stimulation are not due to monosynaptic excitation, but mediated via striatal or cortical routes. Through these routes, CM stimulation with small currents may eventually engage large portions of the striatum, and trigger complex response patterns of striatal neurons [64b].

Figure 4
Responses of striatal neurons to CM stimulation. (A-C) Peri-stimulus raster and rate diagrams of two MSNs (called PANs, A, B) and one interneuron (called TANs, C), in response to CM stimulation. Stimuli were applied at 100 Hz, during the shaded period. ...

In vitro data from sagittal slices of young rat brains that partly preserve the integrity of the Pf-striatal projections showed that both NMDA and non-NMDA receptors mediate thalamic and cortical excitatory effects in more than half of the striatal projection neurons [84, see also 13,24]. These preliminary observations also suggested interesting differences in short term plasticity and probability of neurotransmitter release between corticostriatal and thalamostriatal projections [17a;84]. In this in vitro preparation, thalamic stimulation, but not cortical stimulation, can generate burst-pause pattern of activity in cholinergic interneurons, which differentially gates corticostriatal signaling through striatopallidal and striatonigral pathways [17b].

CM/Pf NEURONAL LOSS IN NEURODEGENERATIVE DISEASES

Significant neuronal loss has been found in the CM/Pf of patients with progressive supranuclear palsy, Huntington's disease or Parkinson's disease [27,28,29]. In parkinsonian patients, subpopulations of parvalbumin-containing neurons are mainly affected in Pf, while in CM non-parvalbumin/non-calbindin neurons are specifically targeted [29]. In rodents, there is controversy as to whether unilateral 6-OHDA lesion of the dopaminergic nigrostriatal pathway induces Pf neurodegeneration; while some authors could not find evidence for neuronal loss in the ipsilateral Pf three months after nigrostriatal dopaminergic lesion, another recent study demonstrated more than 50% loss of Pf neurons projecting to the dopamine-depleted striatum one month after the lesion [28,29]. Systemic MPTP administration also induces significant loss of midline and intralaminar nuclei in mice [20b]. Recent imaging data reported significant changes in the shape, but not the volume, of thalami between parkinsonian patients and controls [58a].

CM/Pf NEURONAL ACTIVITY IN PARKINSON'S DISEASE

There is limited information available on changes of neuronal activity in CM/Pf of dopamine-depleted parkinsonians. Pf firing rates are transiently decreased in anesthetized dopamine-depleted rats [64c], while MPTP exposure in monkeys leads to small changes in glucose utilization in CM/Pf [65a]. A significant reduction in GABA level has been measured in postmortem CM/Pf tissue of patients with Parkinson's disease [23]. The CM/Pf neuronal activity is locked to rest tremor or voluntary movements in parkinsonian patients, consistent with strong ascending proprioceptive influences reaching CM/Pf from brainstem and spinal cord [2,52].

NEUROSURGICAL THALAMIC INTERVENTIONS FOR BRAIN DISEASES

Neurosurgical treatment have long been aimed at the thalamus to treat movement disorders and other diseases. The first stereotaxic thalamotomies in humans targeted the mediodorsal nucleus for the treatment of psychiatric diseases. The ventral anterior and centre median nuclei were later found to be suitable lesion sites for the treatment of psychosis or compulsive and aggressive behavior, respectively. The CM/Pf and adjacent thalamic nuclei also became targets of choice for the alleviation of pain syndromes.

Hassler and Riechert first reported the use of thalamic lesions as treatment for rigidity and tremor in Parkinson's disease [26a]. These influential studies made thalamic surgeries the treatment of choice for Parkinson's diseases and other brain diseases, until the introduction of novel and highly effective pharmacotherapies for these disorders in the late 1960's. Due to the realization that drug therapy may have significant side effects, these procedures were largely abandonded in the 1970s and `80s, but were then re-introduced with safer neurosurgical techniques stereotaxic functional surgeries after it had become clear that pharmacotherapies often have substantial long-time side effects.,Development of electrical macro-stimulation (deep brain stimulation, DBS) as a potentially reversible and adjustable form of surgical treatment of movement disorders, such as Parkinson's disease, dystonia and tremor and other conditions, has also had a major impact.

The primary application of DBS in parkinsonian patients is the treatment of disabling tremor. DBS at the border of the Vop and Vim results in significant reduction of both parkinsonian and essential tremors, with few side effects. Several studies have also described benefits of DBS of CM/Pf in Parkinson's disease [10,10a]. In older studies, CM/Pf-DBS appears to have specifically anti-dyskinetic effects [42], but more recently [55a], CM/Pf-DBS was found to be also effective against freezing of gait, a symptom that is poorly responsive to DBS at other targets. Tremor also seems to be significantly alleviated with CM DBS in advanced PD patients [68].

CM/Pf-DBS is also an effective treatment for Tourette's syndrome [63,93] being effective in reducing the quantity and intensity of tics by 70-90%, and also significantly reduce the psychiatric symptoms of the disease [31,63,78].

References

1a. Adams JE, Rutkin BB. Lesions of the centrum medianum in the treatment of movement disorders. Confin. Neurol. 1965;26:231–45. [PubMed]
1. Aosaki T, Graybiel AM, Kimura M. Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys. Science. 1994;265:412–415. [PubMed]
2. Apkarian AV, Hodge CJ. Primate spinothalamic pathways: II. The cells of origin of the dorsolateral and ventral spinothalamic pathways. J. Comp. Neurol. 1989;288:474–492. [PubMed]
3. Aymerich MS, Barroso-Chinea P, Perez-Manso M, Munoz-Patino AM, Moreno-Igoa M, Gonzalez-Hernandez T, Lanciego JL. Consequences of unilateral nigrostriatal denervation on the thalamostriatal pathway in rats. Eur. J. Neurosci. 2006;23:2099–2108. [PubMed]
4. Bacci J-J, Kachidian P, Kerkerian-LeGoff L, Salin P. Intralaminar thalamic nuclei lesions: Widespread impact on dopamine denervation-mediated cellular defects in the rat basal ganglia. J. Neuropathol. Exp. Ther. 2004;63:20–31. [PubMed]
5. Bamford NS, Zhang H, Schmitz Y, Wu NP, Cepeda C, Levine MS, Schmauss C, Zakharenko SS, Zablow L, Sulzer D. Heterosynaptic dopamine neurotransmission selects sets of corticostriatal terminals. Neuron. 2004;42:653–663. [PubMed]
6. Barroso-Chinea P, Aymerich MS, Castle MM, Perez-Manso M, Tunon T, Erro E, Lanciego JL. Detection of two different mRNAs in a single section by dual in situ hybridization: a comparison between colorimetric and fluorescent detection. J. Neurosci. Methods. 2007;162:119–128. [PubMed]
7. Barroso-Chinea P, Castle M, Aymerich MS, Perez-Manso M, Erro E, Tunon T, Lanciego JL. Expression of the mRNAs encoding for the vesicular glutamate transporters 1 and 2 in the rat thalamus. J. Comp. Neurol. 2007;501:703–715. [PubMed]
7a. Barroso-Chinea P, Castle M, Aymerich MS, Lanciego JL. Expression of vesicular glutamate transporters 1 and 2 in the cells of origin of the rat thalamostriatal pathway. J. Chem. Neuroanat. 2008;35:101–107. [PubMed]
8. Becquet D, Faudon M, Hery F. Effects of thalamic lesion on the bilateral regulation of serotoninergic transmission in rat basal ganglia. Journal of Neural Transmission. 1988;74:117–28. [PubMed]
9. Berendse HW, Groenewegen HJ. Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum. J. Comp. Neurol. 1990;299:187–228. [PubMed]
10. Caparros-Lefebvre D, Blond S, Feltin MP, Pollak P, Benabid AL. Improvement of levodopa induced dyskinesias by thalamic deep brain stimulation is related to slight variation in electrode placement: possible involvement of the centre median and parafascicularis complex. J. Neurol. Neurosurg. Psychiatry. 1999;67:308–314. [PMC free article] [PubMed]
10a. Caparros-Lefebvre D, Pollak P, Feltin MP, Blond S, Benabid AL. The effect of thalamic stimulation on levodopa induced dyskinesias--evaluation of a new target: the center parafascicular median. Revue Neurologique. 1999;155:543–50. [PubMed]
11. Castle M, Aymerich MS, Sanchez-Escobar C, Gonzalo N, Obeso JA, Lanciego JL. Thalamic innervation of the direct and indirect basal ganglia pathways in the rat: Ipsi- and contralateral projections. J. Comp. Neurol. 2005;483:143–153. [PubMed]
12. Cheramy A, Chesselet MF, Romo R, Leviel V, Glowinski J. Effects of unilateral electrical stimulation of various thalamic nuclei on the release of dopamine from dendrites and nerve terminals of neurons of the two nigrostriatal dopaminergic pathways. Neuroscience. 1983;8:767–780. [PubMed]
13. Consolo S, Baldi G, Giorgi S, Nannini L. The cerebral cortex and parafascicular thalamic nucleus facilitate in vivo acetylcholine release in the rat striatum through distinct glutamate receptor subtypes. Eur. J. Neurosci. 1996;8:2702–2710. [PubMed]
13a. Cragg SJ. Meaningful silences: how dopamine listens to the Ach pause. Trends in Neurosci. 2006;29:125–131. [PubMed]
14. Crosson B. Subcortical mechanisms in language: lexical-semantic mechanisms and the thalamus. Brain Cogn. 1999;40:414–38. [PubMed]
15. Deleu D, Lagopoulos M, Louon A. Thalamic hand dystonia: an MRI anatomoclinical study. Acta Neurol. Belg. 2000;100:237–41. [PubMed]
16. Deschênes M, Bourassa J, Doan VD, Parent A. A single-cell study of the axonal projections arising from the posterior intralaminar thalamic nuclei in the rat. Eur. J. Neurosci. 1996;8:329–343. [PubMed]
17. Deschenes M, Bourassa J, Parent A. Striatal and cortical projections of single neurons from the central lateral thalamic nucleus in the rat. Neuroscience. 1996;72:679–687. [PubMed]
17a. Ding J, Surmeier DJ. Neurosci. Meeting Planner. Soc. Neurosci.; Atlanta, GA: 2006. Loss of corticostriatal synapses onto striatopallidal medium spiny neurons after dopamine depletion, Program No. 56.58.
17b. Ding J, Surmeier DJ. Neurosci. Meeting Planner. Soc. Neurosci.; San Diego, CA: 2007. Thalamic gating of corticostriatal signaling mediated by cholinergic interneurons, Program No. 514.7/SS21.
18. Dube L, Smith AD, Bolam JP. Identification of synaptic terminals of thalamic or cortical origin in contact with distinct medium-size spiny neurons in the rat neostriatum. J. Comp. Neurol. 1988;267:455–471. [PubMed]
19. Francois C, Percheron G, Parent A, Sadikot AF, Fenelon G, Yelnik J. Topography of the projection from the central complex of the thalamus to the sensorimotor striatal territory in monkeys. J. Comp. Neurol. 1991;305:17–34. [PubMed]
20. Fremeau RT, Jr, Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR, Storm-Mathisen J, Reimer RJ, Chaudhry FA, Edwards RH. The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc. Natl. Acad. Sci. U S A. 2002;99:14488–14493. [PMC free article] [PubMed]
20a. Fremeau RT, Jr, Voglmaier S, Seal RP, Edwards RH. VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Trends Neurosci. 2004;27:98–103. [PubMed]
20b. Freyaldenhoven TE, Ali SF, Schmued LC. Systemic administration of MPTP induces thalamic neuronal degeneration in mice. Brain Res. 1997;759:9–17. [PubMed]
21. Fujiyama F, Unzai T, Nakamura K, Nomura S, Kaneko T. Difference in organization of corticostriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum. Eur. J. Neurosci. 2006;24:2813–2824. [PubMed]
22. Gao DM, Jeaugey L, Pollak P, Benabid AL. Intensity-dependent nociceptive responses from presumed dopaminergic neurons of the substantia nigra, pars compacta in the rat and their modification by lateral habenula inputs. Brain Res. 1990;529:315–319. [PubMed]
23. Gerlach M, Gsell W, Kornhuber J, Jellinger K, Krieger V, Pantucek F, Vock R, Riederer P. A post mortem study on neurochemical markers of dopaminergic, GABA-ergic and glutamatergic neurons in basal gangliathalamocortical circuits in Parkinson syndrome. Brain Res. 1996;741:142–152. [PubMed]
24. Giorgi S, Rimoldi M, Consolo S. Parafascicular thalamic nucleus deafferentation reduces c-fos expression induced by dopamine D-1 receptor stimulation in rat striatum. Neuroscience. 2001;103:653–661. [PubMed]
24A. Gras C, Herzog E, Bellenchi GCV, Bernard V, Ravassard P, Pohl M, Gasnier B, El Mestikawy S. A third vesicular glutamate transporter expressed by cholinergic and serotonergic neurons. J. Neurosci. 2002;22:5442–5451. [PubMed]
25. Groenewegen HJ, Berendse HW. The specificity of the nonspecific midline and intralaminar thalamic nuclei. Trends Neurosci. 1994;17:52–57. [PubMed]
26. Haber S, McFarland NR. The place of the thalamus in frontal cortical-basal ganglia circuits. Neuroscientist. 2001;7:315–324. [PubMed]
27. Heinsen H, Rub U, Gangnus D, Jungkunz G, Bauer M, Ulmar G, Bethke B, Schuler M, Bocker I, Eisenmenger W, Gotz M, Strik M. Nerve cell loss in thalamic centromedian-parafascicular complex in patients with Huntington's disease. Acta Neuropathol. 1996;91:161–168. [PubMed]
28. Henderson JM, Carpenter K, Cartwright H, Halliday GM. Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson's disease: clinical and therapeutic implications. Brain. 2000;123(Pt 7):1410–1421. [PubMed]
29. Henderson JM, Carpenter K, Cartwright H, Halliday GM. Degeneration of the centre median-parafascicular complex in Parkinson's disease. Ann. Neurol. 2000;47:345–352. [PubMed]
30. Henderson JM, Schleimer SB, Allbutt H, Dabholkar V, Abela D, Jovic J, Quinlivan M. Behavioural effects of parafascicular thalamic lesions in an animal model of parkinsonism. Behav. Brain Res. 2005;162:222–232. [PubMed]
31. Houeto JL, Karachi C, Mallet L, Pillon B, Yelnik J, Mesnage V, Welter ML, Navarro S, Pelissolo A, Damier P, Pidoux B, Dormont D, Cornu P, Agid Y. Tourette's syndrome and deep brain stimulation. J. Neurol. Neurosurg. Psychiatry. 2005;76:992–995. [PMC free article] [PubMed]
32. Ingham CA, Hood SH, Arbuthnott GW. Spine density on neostriatal neurones changes with 6-hydroxydopamine lesions and with age. Brain Res. 1989;503:334–338. [PubMed]
33. Ingham CA, Hood SH, Taggart P, Arbuthnott GW. Plasticity of synapses in the rat neostriatum after unilateral lesion of the nigrostriatal dopaminergic pathway. J. Neurosci. 1998;18:4732–4743. [PubMed]
34. Jones MW, Kilpatrick IC, Phillipson OT. Regulation of dopamine function in the prefrontal cortex of the rat by the thalamic mediodorsal nucleus. Brain Res. Bull. 1987;19:9–17. [PubMed]
35. Jones MW, Kilpatrick IC, Phillipson OT. Thalamic control of subcortical dopamine function in the rat and the effects of lesions applied to the medial prefrontal cortex. Brain Res. 1988;475:8–20. [PubMed]
36. Kashani A, Betancur C, Giros B, Hirsch E, El Mestikawy S. Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease. Neurobiol. Aging. 2007;28:568–578. [PMC free article] [PubMed]
37. Kilpatrick IC, Phillipson OT. Thalamic control of dopaminergic functions in the caudate-putamen of the rat--I. The influence of electrical stimulation of the parafascicular nucleus on dopamine utilization. Neuroscience. 1986;19:965–978. [PubMed]
38. Kilpatrick IC, Jones MW, Johnson BJ, Cornwall J, Phillipson OT. Thalamic control of dopaminergic functions in the caudate-putamen of the rat--II. Studies using ibotenic acid injection of the parafascicular-intralaminar nuclei. Neuroscience. 1986;19:979–990. [PubMed]
39. Kilpatrick IC, Jones MW, Pycock CJ, Riches I, Phillipson OT. Thalamic control of dopaminergic functions in the caudate-putamen of the rat--III. The effects of lesions in the parafascicular-intralaminar nuclei on D2 dopamine receptors and high affinity dopamine uptake. Neuroscience. 1986;19:991–1005. [PubMed]
40. Kimura M, Minamimoto T, Matsumoto N, Hori Y. Monitoring and switching of cortico-basal ganglia loop functions by the thalamo-striatal system. Neurosci. Res. 2004;48:355–360. [PubMed]
41. Kinomura S, Larsson J, Gulyas B, Roland PE. Activation by attention of the human reticular formation and thalamic intralaminar nuclei. Science. 1996;271:512–515. [PubMed]
42. Krauss JK, Pohle T, Weigel R, Burgunder JM. Deep brain stimulation of the centre median-parafascicular complex in patients with movement disorders. J. Neurol. Neurosurg. Psychiatry. 1996;72:546–548. [PMC free article] [PubMed]
43. Krystkowiak P, Martinat P, Defebvre L, Pruvo JP, Leys D, Destee A. Dystonia after striatopallidal and thalamic stroke: clinicoradiological correlations and pathophysiological mechanisms. J. Neurol. Neurosurg. Psychiatry. 1998;65:703–8. [PMC free article] [PubMed]
44. Lacey CJ, Boyes J, Gerlach O, Chen L, Magill PJ, Bolam JP. GABA(B) receptors at glutamatergic synapses in the rat striatum. Neuroscience. 2005;136:1083–1095. [PubMed]
45. Lacey CJ, Bolam JP, Magill PJ. Novel and distinct operational principles of intralaminar thalamic neurons and their striatal projections. J. Neurosci. 2007;27:4374–4384. [PubMed]
46. Lanciego JL, Gonzalo N, Castle M, Sanchez-Escobar C, Aymerich MS, Obeso JA. Thalamic innervation of striatal and subthalamic neurons projecting to the entopeduncular nucleus. Eur. J. Neurosci. 2004;19:1267–1277. [PubMed]
47. Lanciego JL, Rodriguez-Oroz MC, Blesa FJ, Alvarez-Erviti L, Guridi J, Barroso-Chinea P, Smith Y, Obeso JA. Lesion of the centromedian thalamic nucleus in MPTP-treated monkeys. Mov. Disord. 2008;23:708–715. [PubMed]
48. Lapper SR, Bolam JP. Input from the frontal cortex and the parafascicular nucleus to cholinergic interneurons in the dorsal striatum of the rat. Neuroscience. 1992;51:533–545. [PubMed]
49. Lapper SR, Smith Y, Sadikot AF, Parent A, Bolam JP. Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey. Brain Res. 1992;580:215–224. [PubMed]
50. Lievens JC, Bernal F, Forni C, Mahy N, Kerkerian-Le Goff L. Characterization of striatal lesions produced by glutamate uptake alteration: cell death, reactive gliosis, and changes in GLT1 and GADD45 mRNA expression. Glia. 2000;29:222–232. [PubMed]
51. Lievens JC, Salin P, Had-Aissouni L, Mahy N, Kerkerian-Le Goff L. Differential effects of corticostriatal and thalamostriatal deafferentation on expression of the glutamate transporter GLT1 in the rat striatum. J. Neurochem. 2000;74:909–919. [PubMed]
52. Magnin M, Morel A, Jeanmonod D. Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience. 2000;96:549–564. [PubMed]
53. Manabe Y, Kashihara K, Ota T, Shohmori T, Abe K. Motor neglect following left thalamic hemorrhage: a case report. J. Neurol. Sci. 1999;171:69–71. [PubMed]
54. Matsumoto N, Minamimoto T, Graybiel AM, Kimura M. Neurons in the thalamic CM-Pf complex supply striatal neurons with information about behaviorally significant sensory events. J. Neurophysiol. 2001;85:960–976. [PubMed]
55. Matsumoto M, Hikosaka O. Lateral habenula as a source of negative reward signals in dopamine neurons. Nature. 2007;447:1111–1115. [PubMed]
55a. Mazzone P, Stocchi F, Galati S, Insola A, Altibrandi MG, Modugno N, Tropepi D, Brusa L, Stefani A. Bilateral implantation of centromedianparafascicularis complex and GPi: a new combination of unconventional targets for deep brain stimulation in severe Parkinson disease. Neuromodulation. 2006;9:221–228. [PubMed]
56. McFarland NR, Haber SN. Organization of thalamostriatal terminals from the ventral motor nuclei in the macaque. J. Comp. Neurol. 2001;429:321–336. [PubMed]
57. McFarland NR, Haber SN. Convergent inputs from thalamic motor nuclei and frontal cortical areas to the dorsal striatum in the primate. J. Neurosci. 2000;2:3798–3813. [PubMed]
58. McHaffie JG, Stanford TR, Stein BE, Coizet V, Redgrave P. Subcortical loops through the basal ganglia. Trends Neurosci. 2005;28:401–407. [PubMed]
58a. McKeown MJ, Uthama A, Abugharbieh R, Palmer S, Lewis M, Huang X. Shape (but not volume) changes in the thalami in Parkinson's disease. BMC Neurology. 2008;8:8. [PMC free article] [PubMed]
59. Mengual E, de las Heras S, Erro E, Lanciego JL, Gimenez-Amaya JM. Thalamic interaction between the input and the output systems of the basal gangliam. J. Chem. Neuroanat. 1999;16:187–200. [PubMed]
60. Meredith GE, Wouterlood FG. Hippocampal and midline thalamic fibers and terminals in relation to the choline acetyltransferase-containing neurons in the nucleus accumbens of the rat: a light and electron microscopic study. J. Comp. Neurol. 1990;296:204–221. [PubMed]
61. Minamimoto T, Kimura M. Participation of the thalamic CM-Pf complex in attentional orienting. J. Neurophysiol. 2002;87:3090–3101. [PubMed]
62. Minamimoto T, Hori Y, Kimura M. Complementary process to response bias in the centromedian nucleus of the thalamus. Science. 2005;308:1798–1801. [PubMed]
63. Mink JW, Walkup J, Frey KA, Como P, Cath D, Delong MR, Erenberg G, Jankovic J, Juncos J, Leckman JF, Swerdlow N, Visser-Vandewalle V, Vitek JL. Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome. Mov. Disord. 2006;21:1831–1838. [PubMed]
64. Mori E, Yamadori A, Mitani Y. Left thalamic infarction and disturbance of verbal memory: a clinicoanatomical study with a new method of computed tomographic stereotaxic lesion localization. Ann. Neurol. 1986;20:671–676. [PubMed]
64a. Moss J, Bolam JP. The relationship between cortical, thalamic and nigral terminals in the striatum. Proc. 9th International Meeting of the International Basal Ganglia Society Abstr P-025.2007. p. 76.
64b. Nanda BN, Galvan A, Smith Y, Wichmann T. Effects of high frequency stimulation of the centromedian nucleus of thalamus on neuronal activity in the monkey striatum. Proc. 9th International Meeting of the International Basal Ganglia Society Abstr P-129.2007. p. 134.
64c. Ni ZG, Gao DM, Benabid AL, Benazzouz A. Unilateral lesion of the nigrostriatal pathway induces a transient decrease of firing rate with no change in the firing pattern of neurons of the parafascicular nucleus in the rat. Neuroscience. 2000;101:993–999. [PubMed]
65. Nieoullon A, Scarfone E, Kerkerian L, Errami M, Dusticier N. Changes in choline acetyltransferase, glutamic acid decarboxylase, high-affinity glutamate uptake and dopaminergic activity induced by kainic acid lesion of the thalamostriatal neurons. Neurosci. Lett. 1985;58:299–304. [PubMed]
65a. Palombo E, Porrino LJ, Bankiewicz KS, Crane AM, Sokoloff L, Kopin IJ. Local cerebral glucose utilization in monkeys with hemiparkinsonism induced by intracarotid infusion of the neurotoxin MPTP. J. Neurosci. 1990;10:860–869. [PubMed]
66. Parent A, Hazrati LN. Functional anatomy of the basal ganglia. I. The cortico-basal-thalamo-cortical loop. Brain Res. Rev. 1995;20:91–127. [PubMed]
67. Parent M, Parent A. Single-axon tracing and three-dimensional reconstruction of centre median-parafascicular thalamic neurons in primates. J. Comp. Neurol. 2005;481:127–144. [PubMed]
68. Peppe A, Gasbarra A, Stefani A, Chiavalon C, Pierantozz M, Fermi E, Stanzione P, Caltagirone C, Mazzone P. Deep brain stimulation of CM/PF of thalamus could be the new elective target for tremor in advanced Parkinson's Disease? Parkinsonism Relat. Disord. 2008 [PubMed]
69. Powell TPS, Cowan WM. A study of thalamo-striate relations in the monkey. Brain. 1956;79:364–390. [PubMed]
70. Raju DV, Shah DJ, Wright TM, Hal RA, Smith Y. Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats. J. Comp. Neurol. 2006;499:231–243. [PMC free article] [PubMed]
71. Raju DV, Ahern TH, Shah DJ, Wright TM, Standaert DG, Hall RA, Smith Y. Differential synaptic plasticity of the corticostriatal and thalamostriatal systems in an MPTP-treated monkey model of parkinsonism. Eur. J. Neurosci. 2008;27:1647–1658. [PubMed]
71a. Raju DV, Smith Y. Differential localization of vesicular glutamate transporters 1 and 2 in the rat striatum. In: Bolam JP, Ingham CA, Magill PJ, editors. The Basal Ganglia VIII. Springer; New York: pp. 601–610.
72. Romo R, Cheramy A, Desban M, Godeheu G, Glowinski J. GABA in the intralaminar thalamic nuclei modulates dopamine release from the two dopaminergic nigro-striatal pathways in the cat. Brain Res. Bull. 1983;11:671–80. [PubMed]
73. Royce GJ. Single thalamic neurons which project to both the rostral cortex and caudate nucleus studied with the fluorescent double labeling method. Exp. Neurol. 1983;79:773–784. [PubMed]
73a. Rudskin TM, Sadikot AF. Thalamic input to parvalbumin-immunoreactive GABAergic interneurons: organization in normal striatum and effect of neonatal decortication. Neuroscience. 1999;88:1165–1175. [PubMed]
74. Sadikot AF, Parent A, Smith Y, Bolam JP. Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity. J. Comp. Neurol. 1992;320:228–242. [PubMed]
75. Sadikot AF, Parent A, Francois C. Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: A PHA-L study of subcortical projections. J. Comp. Neurol. 1992;315:137–159. [PubMed]
76. Salin P, Kachidian P. Thalamo-striatal deafferentation affects preproenkephalin but not preprotachykinin gene expression in the rat striatum. Mol. Brain Res. 1998;57:257–265. [PubMed]
77. Samuel D, Kerkerian-Le Goff L, Kumar U, Errami M, Scarfone E, Nieoullon A. Changes in striatal cholinergic, gabaergic, dopaminergic and serotoninergic biochemical markers after kainic acid-induced thalamic lesions in the rat. J. Neural Transm. Park. Dis. Dement. Sect. 1990;2:193–203. [PubMed]
78. Servello D, Porta M, Sassi M, Brambilla A, Robertson MM. Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. J. Neurol. Neurosurg. Psychiatry. 2008;79:136–142. 2008. [PubMed]
79. Sidibé M, Bevan MD, Bolam JP, Smith Y. Efferent connections of the internal globus pallidus in the squirrel monkey: I. Topography and synaptic organization of the pallidothalamic projection. J. Comp. Neurol. 1997;382:323–347. [PubMed]
80. Sidibe M, Pare JF, Raju DV, Smith Y. Anatomical and functional relationships between intralaminar thalamic nuclei and basal ganglia in monkeys. In: Nicholson LFB, Faull RLM, editors. The Basal Ganglia VII. Kluwer Academic/Plenum; New York: 2002. pp. 409–420.
81. Sidibe M, Pare JF, Smith Y. Nigral and pallidal inputs to functionally segregated thalamostriatal neurons in the centromedian/parafascicular intralaminar nuclear complex in monkey. J. Comp. Neurol. 2002;447:286–299. [PubMed]
82. Sidibe M, Smith Y. Differential synaptic innervation of striatofugal neurones projecting to the internal or external segments of the globus pallidus by thalamic afferents in the squirrel monkey. J. Comp. Neurol. 1996;365:445–465. [PubMed]
83. Sidibé M, Smith Y. Thalamic inputs to striatal interneurons in monkeys: Synaptic organization and co-localization of calcium binding proteins. Neuroscience. 1999;89:1189–1208. [PubMed]
84. Smeal RM, Gaspar RC, Keefe KA, Wilcox KS. A rat brain slice preparation for characterizing both thalamostriatal and corticostriatal afferents. J. Neurosci. Methods. 2007;159:224–235. [PubMed]
85. Smith AD, Bolam JP. The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurons. Trends Neurosci. 1990;13:259–265. [PubMed]
86. Smith Y, Bennett BD, Bolam JP, Parent A, Sadikot AF. Synaptic relationships between dopaminergic afferents and cortical or thalamic input at the single cell level in the sensorimotor territory of the striatum in monkey. J. Comp. Neurol. 1994;344:1–19. [PubMed]
87. Smith Y, Parent A. Differential connections of caudate nucleus and putamen in the squirrel monkey (Saimiri sciureus) Neuroscience. 1986;18:347–371. [PubMed]
88. Smith Y, Raju DV, Pare JF, Sidibe M. The thalamostriatal system: a highly specific network of the basal ganglia circuitry. Trends Neurosci. 2004;27:520–527. [PubMed]
89. Stephens B, Mueller AJ, Shering AF, Hood SH, Taggart P, Arbuthnott GW, Bell JE, Kilford L, Kingsbury AE, Daniel SE, Ingham CA. Evidence of a breakdown of corticostriatal connections in Parkinson's disease. Neuroscience. 2005;132:741–754. [PubMed]
90. Thomas TM, Smith Y, Levey AI, Hersch SM. Cortical inputs to m2-immunoreactive striatal interneurons in rat and monkey. Synapse. 2000;37:252–261. [PubMed]
91. Van der Werf YD, Witter MP, Groenewegen HJ. The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res. Rev. 2002;39:107–140. [PubMed]
92. Villalba RM, Lee H, Raju DV, Smith Y. Striatal dopaminergic denervation and spine loss in MPTP-treated monkeys. In: Groenewegen HJ, Berendse HJ, editors. The Basal Ganglia IX. Springer; New York: in press.
93. Visser-Vandewalle V, Temel Y, Boon P, Vreeling F, Colle H, Hoogland G, Groenewegen HJ, van der Linden C. Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome, Report of three cases. J. Neurosurg. 2003;99:1094–1100. [PubMed]
94. Vogt C, Vogt O. Thalamusstudien I-III. I. Zur Einfurung, II. Homogenitat und Grenzgestaldung der Grisea des Thalamus, III. Griseum centrale (centrum medianum Luys) J. Physiol. Neurol. Lpz. 1941;50:31–154.
95. Wang Z, Kai L, Day M, Ronesi J, Yin HH, Ding J, Tkatch T, Lovinger DM, Surmeier DJ. Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons. Neuron. 2006;50:443–452. [PubMed]
96. Watson RT, Valenstein E, Heilman KM. Thalamic neglect. Possible role of the medial thalamus and nucleus reticularis in behavior. Arch. Neurol. 1981;38:501–506. [PubMed]
97. Weigel R, Krauss JK. Center median-parafascicular complex and pain control. Review from a neurosurgical perspective. Stereotact. Funct. Neurosurg. 2004;82:115–126. [PubMed]
97a. Young RF. Functional neurosurgery with the Leksell Gamma knife. Stereotact Funct Neurosurg. 1996;66:19–23. [PubMed]
98. Zackheim J, Abercrombie ED. Thalamic regulation of striatal acetylcholine efflux is both direct and indirect and qualitatively altered in the dopamine-depleted striatum. Neuroscience. 2005;131:423–436. [PubMed]
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...